AIM To investigate potential effects of poly I:C on mucosal injury and epithelial barrier disruption in dextran sulfate sodium(DSS)-induced acute colitis.METHODS Thirty C57BL/6 mice were given either regular drinking ...AIM To investigate potential effects of poly I:C on mucosal injury and epithelial barrier disruption in dextran sulfate sodium(DSS)-induced acute colitis.METHODS Thirty C57BL/6 mice were given either regular drinking water(control group) or 2%(w/v) DSS drinking water(model and poly I:C groups) ad libitum for 7 d. Poly I:C was administrated subcutaneously (20 μg/mouse) 2 h prior to DSS induction in mice of the poly I:C group. Severity of colitis was evaluated by disease activity index, body weight, colon length, histology and myeloperoxidase (MPO) activity, as well as the production of proinflammatory cytokines, including tumor necrosis factor-α(TNF-α), interleukin 17(IL-17) and interferon-γ (IFN-γ). Intestinal permeability was analyzed by the fluorescein isothiocyanate labeleddextran (FITC-D) method. Ultrastructural features of the colon tissue were observed under electron microscopy. Expressions of tight junction(TJ) proteins, including zo-1, occludin and claudin-1, were measured by immunohistochemistry/immunofluorescence, Western blot and real-time quantitative polymerase chain reaction(RT-qPCR).RESULTS DSS caused significant damage to the colon tissue in the model group. Administration of poly I:C dramatically protected against DSS-induced colitis, as demonstrated by less body weight loss, lower disease activity index score, longer colon length, colonic MPO activity, and improved macroscopic and histological scores. It also ameliorated DSS-induced ultrastructural changes of the colon epithelium, as observed under scanning electron microscopy, as well as FITC-D permeability. The m RNA and protein expressions of TJ protein, zo-1, occludin and claudin-1 were also found to be significantly enhanced in the poly I:C group, as determined by immunohistochemistry/immunofluorescence, Western blot and RT-q PCR. By contrast, poly I:C pretreatment markedly reversed the DSS-induced up-regulated expressions of the inflammatory cytokines TNF-α, IL-17 and IFN-γ.CONCLUSION Our study suggested that poly I:C may protect against DSS-induced colitis through maintaining integrity of the epithelial barrier and regulating innate immune responses, which may shed light on the therapeutic potential of poly I:C in human colitis.展开更多
基金the Scientific Research Foundation of HealthDepartment of Hebei Province,No.20160483
文摘AIM To investigate potential effects of poly I:C on mucosal injury and epithelial barrier disruption in dextran sulfate sodium(DSS)-induced acute colitis.METHODS Thirty C57BL/6 mice were given either regular drinking water(control group) or 2%(w/v) DSS drinking water(model and poly I:C groups) ad libitum for 7 d. Poly I:C was administrated subcutaneously (20 μg/mouse) 2 h prior to DSS induction in mice of the poly I:C group. Severity of colitis was evaluated by disease activity index, body weight, colon length, histology and myeloperoxidase (MPO) activity, as well as the production of proinflammatory cytokines, including tumor necrosis factor-α(TNF-α), interleukin 17(IL-17) and interferon-γ (IFN-γ). Intestinal permeability was analyzed by the fluorescein isothiocyanate labeleddextran (FITC-D) method. Ultrastructural features of the colon tissue were observed under electron microscopy. Expressions of tight junction(TJ) proteins, including zo-1, occludin and claudin-1, were measured by immunohistochemistry/immunofluorescence, Western blot and real-time quantitative polymerase chain reaction(RT-qPCR).RESULTS DSS caused significant damage to the colon tissue in the model group. Administration of poly I:C dramatically protected against DSS-induced colitis, as demonstrated by less body weight loss, lower disease activity index score, longer colon length, colonic MPO activity, and improved macroscopic and histological scores. It also ameliorated DSS-induced ultrastructural changes of the colon epithelium, as observed under scanning electron microscopy, as well as FITC-D permeability. The m RNA and protein expressions of TJ protein, zo-1, occludin and claudin-1 were also found to be significantly enhanced in the poly I:C group, as determined by immunohistochemistry/immunofluorescence, Western blot and RT-q PCR. By contrast, poly I:C pretreatment markedly reversed the DSS-induced up-regulated expressions of the inflammatory cytokines TNF-α, IL-17 and IFN-γ.CONCLUSION Our study suggested that poly I:C may protect against DSS-induced colitis through maintaining integrity of the epithelial barrier and regulating innate immune responses, which may shed light on the therapeutic potential of poly I:C in human colitis.
